This invention relates to a probe apparatus useful in aspirating a liquid sample container. More particularly this invention relates to a probe apparatus having a probe tip which can completely remove a liquid sample from a suspension containing particulate matter and residue without clogging.
In DNA and peptide synthesis, nucleotides or amino acids are added sequentially to each other on a solid substrate. In the case of peptide synthesis, continuous flow processes of synthesis are available. In these process, a solid support such as polystyrene or polyamide-kieselguhr are positioned in the reaction column through which the reagents, including activated amino acid derivatives in the desired sequence, are passed. The excess reagents are flushed from the column by continuous flow of solvent.
The individual activated amino acid derivatives each are stored in a vial which is covered with a moisture-proof seal such as aluminum foil. It is necessary to utilize such a seal since moisture will deactivate the amino acids and prevent them from coupling to the peptide chain. In the synthesis procedure, the next amino acid to be coupled to the peptide chain is dissolved in a solvent mixed with a catalyst. Once the amino acids are mixed with the catalyst they are stable only for about 2-3 hours. Therefore, each amino acid solution must be prepared immediately prior to use. Approximately one half to one and a half hours is required to couple an amino acid to the peptide chain in the continuous process. Often, suspended particulate matter and residue is generated when the amino acids are dissolved. The particulates and residue must not be introduced into the reaction column because they block the column causing increased back pressure, reduced flow, and a failed synthesis. Therefore, prepared amino acid solutions must be filtered prior to being introduced into the reaction column.
Prior to the present invention, amino acid solutions were prepared manually and then reacted with the previously prepared peptide chain. Obviously, such a method is time consuming and very undesirable. An automated method has been proposed for preparing the amino acid solutions and utilizing the solutions sequentially to form the peptide chain. Automated apparatus exists which in a separate operation can remove a screw cap from a container or pierce a seal on a container containing the activated amino acid derivative. The amino acid is dissolved in a second operation. In a third operation, the amino acid solution is removed from the container by aspiration into a syringe. A filter is then positioned and, finally the solution is introduced through the filter into the reaction zone. This approach is complex, costly and unreliable.
It is desirable to remove substantially all of the amino acid solution from the vial containing the solution since the amino acids are quite expensive.
It would be desirable to provide a means for effecting continuous and automated peptide synthesis in a manner which utilizes substantially all of an amino acid reagent without introducing particulate matter or residue into the reaction column. In addition, it would be desirable to provide such a means wherein clogging with particulate matter and residue is prevented. Furthermore, it would be desirable to provide such a means which is self cleaning so it can be used for successive couplings without carrying contaminants from one amino acid preparation to the next and without requiring replacement of apparatus components such as filter elements during an automated peptide synthesis. Also, it would be desirable to eliminate the need for removing a container cap in order to form an amino acid solution and then subsequently removing the solution from a container in order to effect reaction. It would also be desirable to provide such a means which disperses liquid and gas to a sample container to enable dissolution and mixing.